This domain is often found adjacent to the DHH domain (
), and is called DHHA1 for DHH associated domain. DHHA1 is diagnostic of DHH subfamily 1 members [
]. This domain is also found in alanyl tRNA synthetase (e.g., ), suggesting that it may have an RNA binding function. The domain is about 60 residues long and contains a conserved GG motif.
At least eleven different protein factors are involved in initiation of protein synthesis in eukaryotes. Binding of initiator tRNA and mRNA to the 40S subunit requires the presence of the translation initiation factors eIF-2 and eIF-3, with eIF-3 being particularly important for 80S ribosome dissociation and mRNA binding[
]. eIF-3 is the most complex translation inititation factor, consisting of about 13 putative subunits and having a molecular weight of between 550 - 700kDa in mammalian cells. Subunits are designated eIF-3a - eIF-3m; the large number of subunits means that the interactions between the individual subunits that make up the eIF-3 complex are complex and varied.
This superfamily represents an alpha helical domain found in eIF-3 subunit J proteins. The eIF-3j subunit can bind to the 40S ribosome alone and its binding site overlaps that of the eIF-3 complex [
].
This shows protein subunits of the eukaryotic translation initiation factor 3 J (eIF3j). It is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome [
,
]. In Saccharomyces cerevisiae, eIF3j has been shown to be required for processing of 20S pre-rRNA and binds to 18S rRNA and eIF3 subunits Rpg1p and Prt1p [].
The release factor eRF1 terminates protein biosynthesis by recognising stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known [
]. The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase centre. A conserved groove on domain 1 is proposed to form the codon recognition site [].This entry represents the first domain of eRF1.
This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating
peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known []. The overallshape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop,
aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tipof domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl
transferase centre. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site [].This domain is also found in other proteins for which the precise molecular function is unknown. Many of them are from
Archaebacteria. These proteins may also be involved in translation termination but this awaits experimental verification.
This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating
peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known []. The overallshape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop,
aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tipof domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl
transferase centre. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site [].This domain is also found in other proteins which may also be involved in translation termination
Terminating protein synthesis on the ribosome requires the presence of a class I polypeptide chain release factor (RF) to induce peptidyl-tRNA hydrolysis. Bacteria possess two class I RFs; RF1 which recognises UAG and UAA, and RF2 which recognises UGA and UAA. Mitochondrial RFs are related structurally and functionally to those of bacteria. Eukaryotes posses only a single class 1 factor, eRF1, which recognises all three termination codons. Similarly, in all archaeal species where the complete sequence of the genome is available, only a single class I factor, aRF1, has been identified so far. The aRF1 family is highly homologous to the eRF1 family, indicating a common origin and ancestor molecule. The bacterial and mitochondrial class I RFs show no significant sequence similarity with their eukaryotic and archaeal counterparts and are considered to form a separate family. For more information see [
,
,
].This entry represents the eRF1 and aRF1 proteins.
This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating
peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known []. The overallshape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop,
aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tipof domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl
transferase centre. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site [].This domain is also found in other proteins which may also be involved in translation termination but this awaits experimental verification.
There are four different enzymes that share a similar catalytic mechanism which involves the phosphorylation by ATP (or GTP) of a specific histidine residue in the active site. These enzymes areATP citrate-lyase (
) [
], the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues, catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. ATP-citrate lyase is a tetramer of identical subunits.Succinyl-CoA ligase (GDP-forming) (
) [
] is a mitochondrial enzyme that catalyzes the substrate level phosphorylation step of the tricarboxylic acid cycle: the formation of succinyl-CoA from succinate with a concomitant hydrolysis of GTP to GDP and phosphate. This enzyme is a dimer composed of an alpha and a beta subunits.Succinyl-CoA ligase (ADP-forming) (
) [
] is a bacterial enzyme that during aerobic metabolism functions in the citric acid cycle, coupling the hydrolysis of succinyl-CoA to the synthesis of ATP. It can also function in the other direction for anabolic purposes. This enzyme is a tetramer composed of two alpha and two beta subunits.Malate-CoA ligase (
) (malyl-CoA synthetase) [
], is a bacterial enzyme that forms malyl-CoA from malate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. Malate-CoA ligase is composed of two different subunits.This entry describes succinyl-CoA synthetase alpha subunits, but does not discriminate between GTP-specific and ATP-specific reactions. ATP citrate lyases appear to form an outgroup, and are not included in this entry.
This superfamily represents a structural domain consisting of 3-layers, alpha/beta/alpha. This domain is found in both the alpha and beta chains of succinate--CoA ligase (also known as succinyl-CoA synthase;
(GDP-forming) and
(ADP-forming)) [
,
]. This domain can also be found in ATP citrate synthase (), malate-CoA ligase (
) and acetate-CoA ligase (or acetyl-CoA synthase) (
), as well as bacterial Fdr. Some members of the domain utilise ATP others use GTP.
This entry represents a domain found in both the alpha and beta chains of succinyl-CoA synthase (
(GDP-forming) and
(ADP-forming)) [
,
]. This domain can also be found in ATP citrate synthase () and malate-CoA ligase (
). Some members of the domain utilise ATP others use GTP.
ATP-citrate lyase/succinyl-CoA ligase, active site
Type:
Active_site
Description:
There are four different enzymes that share a similar catalytic mechanism which involves the phosphorylation by ATP (or GTP) of a specific histidine residue in the active site. These enzymes are: ATP citrate-lyase (
) [
], the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues, catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. ATP-citrate lyase is a tetramer of identical subunits; Succinyl-CoA ligase (GDP-forming) () [
] is a mitochondrial enzyme that catalyzes the substrate level phosphorylation step of the tricarboxylic acid cycle: the formation of succinyl-CoA from succinate with a concomitant hydrolysis of GTP to GDP and phosphate. This enzyme is a dimer composed of an alpha and a beta subunits; Succinyl-CoA ligase (ADP-forming) () [
] is a bacterial enzyme that during aerobic metabolism functions in the citric acid cycle, coupling the hydrolysis of succinyl-CoA to the synthesis of ATP. It can also function in the other direction for anabolic purposes. This enzyme is a tetramer composed of two alpha and two beta subunits; and Malate-CoA ligase () (malyl-CoA synthetase) [
], is a bacterial enzyme that forms malyl-CoA from malate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. Malate-CoA ligase is composed of two different subunits.This pattern, which is located some 50 residues to the C-terminal of
, includes the active site phosphorylated histidine residue.
N-linked glycosylation is a ubiquitous protein modification, and is essential for viability in eukaryotic cells. A lipid-linked core-oligosaccharide is assembled at the membrane of the endoplasmic reticulum and transferred to selected asparagine residues of nascent polypeptide chains by the oligosaccharyl transferase (OTase) complex [
].This family consists of the oligsacharyl transferase STT3 subunit and related proteins. The STT3 subunit is part of the oligosccharyl transferase (OTase) complex of proteins and is required for its activity [
]. In eukaryotes, OTase transfers a lipid-linked core-oligosaccharide to selected asparagine residues in the ER. In the archaea STT3 occurs alone, rather than in an OTase complex, and is required for N-glycosylation of asparagines [,
].
Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that regulate heterochromatin formation, developmental timing, defence against parasitic nucleic acids, and genome rearrangement. Many small regulatory RNAs are thought to function in nuclei, and in plants and fungi small interfering RNAs (siRNAs) associate with nascent transcripts and direct chromatin and/or DNA modifications. NRDE-2, is required for siRNA-mediated silencing in nuclei. NRDE-2 associates with the Argonaute protein NRDE-3 within nuclei and is recruited by NRDE-3/siRNA complexes to nascent transcripts that have been targeted by RNA interference, RNAi, the process whereby double-stranded RNA directs the sequence-specific degradation of mRNA [
].
These sequences are all members of the Class IIA subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases. The sequences are restricted to the Gram-negative and primarily alpha proteobacteria. Only one sequence has been annotated as other than "hypothetical."That one, from Brucella, is annotated as related to NagD, but only by sequence similarity and should be treated with some scepticism.
This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes [
]. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins []. WDR83OS/Asterix is the substrate-interacting subunit of the PAT complex, whereas CCDC47 () is required to maintain the stability of WDR83OS/Asterix [
,
]. The PAT complex favors the binding to TMDs with exposed hydrophilic amino acids within the lipid bilayer and provides a membrane-embedded partially hydrophilic environment in which TMD1 binds [].CCDC47 is associated with various membrane-associated processes and is a component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis [
]. It is also involved in the regulation of calcium ion homeostasis in the ER [], being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway [].This entry also includes the uncharacterised proteins YNR021W from S. cerevisiae, C2G5.01 from S. pombe and At5g49945 from Arabidopsis.
Iron-sulphur (FeS) clusters are important cofactors for numerous proteins involved in electron transfer, in redox and non-redox catalysis, in gene regulation, and as sensors of oxygen and iron. These functions depend on the various FeS cluster prosthetic groups, the most common being [2Fe-2S] and [4Fe-4S][
]. FeS cluster assembly is a complex process involving the mobilisation of Fe and S atoms from storage sources, their assembly into [Fe-S]form, their transport to specific cellular locations, and their transfer to recipient apoproteins. So far, three FeS assembly machineries have been identified, which are capable of synthesising all types of [Fe-S] clusters: ISC (iron-sulphur cluster), SUF (sulphur assimilation), and NIF (nitrogen fixation) systems.The ISC system is conserved in eubacteria and eukaryotes (mitochondria), and has broad specificity, targeting general FeS proteins [
,
]. It is encoded by the isc operon (iscRSUA-hscBA-fdx-iscX). IscS is a cysteine desulphurase, which obtains S from cysteine (converting it to alanine) and serves as a S donor for FeS cluster assembly. IscU and IscA act as scaffolds to accept S and Fe atoms, assembling clusters and transferring them to recipient apoproteins. HscA is a molecular chaperone and HscB is a co-chaperone. Fdx is a [2Fe-2S]-type ferredoxin. IscR is a transcription factor that regulates expression of the isc operon. IscX (also known as YfhJ) appears to interact with IscS and may function as an Fe donor during cluster assembly [
].The SUF system is an alternative pathway to the ISC system that operates under iron starvation and oxidative stress. It is found in eubacteria, archaea and eukaryotes (plastids). The SUF system is encoded by the suf operon (sufABCDSE), and the six encoded proteins are arranged into two complexes (SufSE and SufBCD) and one protein (SufA). SufS is a pyridoxal-phosphate (PLP) protein displaying cysteine desulphurase activity. SufE acts as a scaffold protein that accepts S from SufS and donates it to SufA [
]. SufC is an ATPase with an unorthodox ATP-binding cassette (ABC)-like component. SufA is homologous to IscA [], acting as a scaffold protein in which Fe and S atoms are assembled into [FeS]cluster forms, which can then easily be transferred to apoproteins targets.
In the NIF system, NifS and NifU are required for the formation of metalloclusters of nitrogenase in Azotobacter vinelandii, and other organisms, as well as in the maturation of other FeS proteins. Nitrogenase catalyses the fixation of nitrogen. It contains a complex cluster, the FeMo cofactor, which contains molybdenum, Fe and S. NifS is a cysteine desulphurase. NifU binds one Fe atom at its N-terminal, assembling an FeS cluster that is transferred to nitrogenase apoproteins [
]. Nif proteins involved in the formation of FeS clusters can also be found in organisms that do not fix nitrogen [].This entry represents the C-terminal of NifU and homologous proteins. NifU contains two domains: an N-terminal (
) and a C-terminal domain [
]. These domains exist either together or on different polypeptides, both domains being found in organisms that do not fix nitrogen (e.g. yeast), so they have a broader significance in the cell than nitrogen fixation.
This domain is found in the N-terminal region of BOP1-like WD40 proteins. Bop1 is a nucleolar protein involved in rRNA processing, thereby controlling the cell cycle [
]. It is required for the maturation of the 25S and 5.8S ribosomal RNAs. It may serve as an essential factor in ribosome formation that coordinates processing of the spacer regions in pre-rRNA.
This entry represents the WD repeat BOP1/Erb1 family. Members of this family are ribosome biogenesis proteins. In humans and mice, BOP1 is a component of the PeBoW complex (composed of BOP1, PES1 and WDR12), which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome [
]. In Saccharomyces cerevisiae, Erb1 is a component of the NOP7 complex, which is required for maturation of the 25S and 5.8S ribosomal RNAs and formation of the 60S ribosome [
].
NADH:ubiquinone oxidoreductase (complex I) (
) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) [
]. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This entry represents NADH:ubiquinone oxidoreductase, chain 4L, as well as NADH-quinone oxidoreductase (
). In eukaryotes, these enzymes are usually found in either mitochondria or chloroplasts as part of the respiratory-chain NADH dehydrogenase (also known as complex I or NADH-ubiquinone oxidoreductase), an oligomeric enzymatic complex [
]. However, they are also found in bacteria [] and archaea [] where they are annotated as NuoK subunit.
NADH:ubiquinone oxidoreductase (complex I) (
) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) [
]. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This entry represents chain 6 from NADH:ubiquinone oxidoreductase and NADH-plastoquinone oxidoreductase. Bacterial proton-translocating NADH-quinone oxidoreductase (NDH-1) is composed of 14 different subunits. The chain belonging to this family is a subunit that constitutes the membrane sector of the complex. It reduces ubiquinone to ubiquinol utilising NADH. Plant chloroplastic NADH-plastoquinone oxidoreductase reduces plastoquinone to plastoquinol. Mitochondrial NADH-ubiquinone oxidoreductase from a variety of sources reduces ubiquinone to ubiquinol.
Members of this family are PsaC, an essential component of photosystem I (PS-I) reaction centre in Cyanobacteria and chloroplasts. This small protein, about 80 amino acids in length, contains two copies of the ferredoxin-like 4Fe-4S binding site and therefore eight conserved Cys residues. This protein is also called photosystem I subunit VII.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L36 is the smallest protein from the large subunit of the prokaryotic ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities can be grouped into: bacterial L36; algal and plant chloroplast L36; Cyanelle L36. L36 is a small basic and cysteine-rich protein of 37 amino-acid residues.
The isoprenylcysteine o-methyltransferase (
) carries out carboyxl methylation of cleaved eukaryotic proteins that terminate in a CaaX motif. In Saccharomyces cerevisiae, this methylation is carried out by Ste14p, an integral endoplasmic reticulum membrane protein. Ste14p is the founding member of the isoprenylcysteine carboxyl methyltransferase (ICMT) family, whose members share significant sequence homology [
].This entry also includes ICMT from Methanosarcina acetivorans (
). It comprises a core of five transmembrane α-helices and a cofactor-binding pocket enclosed within a highly conserved C-terminal catalytic subdomain [
].
DNA polymerase epsilon is essential for cell viability and chromosomal DNA replication in budding yeast. In addition, DNA polymerase epsilon may be involved in DNA repair and cell-cycle checkpoint control. The enzyme consists of at least four subunits in mammalian cells as well as in yeast. The largest subunit of DNA polymerase epsilon is responsible for polymerase activity. In mouse, the DNA polymerase epsilon subunit B is the second largest subunit of the DNA polymerase. A part of the N-terminal was found to be responsible for the interaction with SAP18. Experimental evidence suggests that this subunit may recruit histone deacetylase to the replication fork to modify the chromatin structure [
].
DNA polymerase epsilon is essential for cell viability and chromosomal DNA replication in budding yeast. In addition, DNA polymerase epsilon may be involved in DNA repair and cell-cycle checkpoint control. The enzyme consists of at least four subunits in mammalian cells as well as in yeast. The largest subunit of DNA polymerase epsilon is responsible for polymerase activity. In mouse, the DNA polymerase epsilon subunit B is the second largest subunit of the DNA polymerase. A part of the N-terminal was found to be responsible for the interaction with SAP18. Experimental evidence suggests that this subunit may recruit histone deacetylase to the replication fork to modify the chromatin structure [
].
This family represents the regulatory subunit of the Rab3GAP complex, also known as Rab3GAP2. Small G proteins of the Rab family are regulators of intracellular vesicle traffic. Their rate of GTP hydrolysis is enhanced by specific GTPase-activating proteins (GAPs) that switch G proteins to their inactive form [
]. Rab3GAP1 (catalytic subunit) has been shown to form a heterodimeric complex with Rab3GAP2 (the regulatory subunit), and this complex acts as a guanosine nucleotide exchange factor for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3GAP complex may participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters [,
]. It also activates Rab18 and promotes autolysosome maturation through the Vps34 Complex I [].Mutations in the Rab3GAP1/2 gene cause Warburg micro syndrome (WMS), a hereditary autosomal neuromuscular disorder [
].
The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.
The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.Med10 is one of the protein subunits of the Mediator complex, tethered to Med14 (Rgr1) protein. Med10 specifically mediates basal-level HIS4 transcription via Gcn4. In addition, there is a putative requirement for Med10 in Bas2-mediated transcription [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The genomic structure and sequence of the human ribosomal protein L7a has been determined and shown to
resemble other mammalian ribosomal protein genes []. The sequence of a gene for ribosomal protein L4 of yeast has also been determined; its single open reading frame is highly similar
to mammalian ribosomal protein L7a [,
]. Several other ribosomal proteins have been found to share sequence similarity with L7a, including Saccharomyces cerevisiae NHP2 [
], Bacillus subtilis hypothetical protein ylxQ, Haloarcula marismortui Hs6, and Methanocaldococcus jannaschii (Methanococcus jannaschii) MJ1203.
Dynein is a multisubunit microtubule-dependent motor enzyme that acts as the force generating protein of eukaryotic cilia and flagella. The cytoplasmic isoform of dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.Dynein is composed of a number of ATP-binding large subunits (see
), intermediate size subunits and small subunits. Among the small subunits, there is a family of highly conserved proteins which make up this family [
,
,
]. Proteins in this family act as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function and may play a role in changing or maintaining the spatial distribution of cytoskeletal structures. In yeast, it was identified as a component of the nuclear pore complex where it may contribute to the stable association of the Nup82 subcomplex with the nuclear pore complex [].Both type 1 (DLC1) and 2 (DLC2) dynein light chains have a similar two-layer α-β core structure consisting of beta-alpha(2)-beta-X-beta(2) [
,
].
This family represents ScpA, which along with ScpB (
) interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation [
,
]. The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli [], where MukB () is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE (
) or MukF (
), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.
In general scpA and scpB form an operon in most bacterial genomes. Flanking genes are highly variable suggesting that the operon has moved throughout evolution. Bacteria containing an smc gene also contain scpA or scpB but not necessarily both. An exception is found in Deinococcus radiodurans, which contains scpB but neither smc nor scpA. In the archaea the gene order SMC-ScpA is conserved in nearly all species, as is the very short distance between the two genes, indicating co-transcription of the both in different archaeal genera and arguing that interaction of the gene products is not confined to the homologues in Bacillus subtilis. It would seem probable that, in light of all the studies, SMC, ScpA and ScpB proteins or homologues act together in chromosome condensation and segregation in all prokaryotes [
].
This entry represents the N-terminal domain of the H2 subunit of the condensing II complex, found in eukaryotes but not in fungi. Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII is concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive phosphorylations, eg, entry of the complex, in Sch.pombe, into the nucleus during mitosis is promoted by Cdk1 phosphorylation of SMC4/Cut3; and it has been shown that Cdk1 phosphorylates CAP-D3 at Thr1415 in He-La cells thus promoting early stage chromosomal condensation by CII [
,
].
RNA polymerase II-associated protein 1, C-terminal
Type:
Domain
Description:
Inhibition of RNA polymerase II-associated protein 1 (RPAP1) synthesis in Saccharomyces cerevisiae (Baker's yeast) results in changes in global gene expression that are similar to those caused by the loss of the RNAPII subunit Rpb11 [
]. This entry represents the C-terminal region that contains the motif GLHHH. This region is conserved from yeast to humans.
RNA polymerase II-associated protein 1, N-terminal
Type:
Domain
Description:
Inhibition of RNA polymerase II-associated protein 1 (RPAP1) synthesis in Saccharomyces cerevisiae (Baker's yeast) results in changes in global gene expression that are similar to those caused by the loss of the RNAPII subunit Rpb11 [
]. This entry represents the N-terminal region of RPAP-1 that is conserved from yeast to humans.
Editase (
) are enzymes that alter mRNA by catalyzing the
site-selective deamination of adenosine residue into inosine residue.The editase domain contains the active site and binds three Zn atoms [
].Several editases share a common global arrangement of domains, from N to C terminus: two
'double-stranded RNA-specific adenosine deaminase' (DRADA) repeat domains, followed bythree 'double-stranded RNA binding' (DsRBD) domains, followed by
the editase domain. Other editases have a simplified domains structure with noDRADA_REP and possibly fewer DSRBD domains. Editase that deaminate cytidine are not detected by this signature.
Remorin binds both simple and complex galaturonides. The N-terminal region of remorin is proline rich, while the C-terminal region has been predicted to form a coiled-coil, that is expected to interact with other macromolecules, most likely DNA. Functional similarities between the behavior of the proteins and viral proteins involved in intercellular communication have been noted [
].
This is the N-terminal domain of transcription termination/antitermination protein NusG, which is involved in transcription elongation, termination and antitermination. It also occurs at the N-terminal of transcription antitermination protein RfaH and in the transcription elongation factor Spt5 [
,
,
,
].
Bestrophin is a 68kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterised by a depressed light peak in the electrooculogram [
]. VMD2 encodes a 585-amino acid protein with an approximate mass of 68kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localised to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak. Bestrophin and other RFP family members represent a new class of calcium-activated chloride channels (CaCC) [], indicating a direct role for bestrophin in generating the light peak [,
,
]. Bestrophins are also permeable to other monovalent anions including bicarbonate, bromine, iodine, thiocyanate an nitrate [,
]. Structural analysis revealed that N-terminal region of the proteins is highly conserved and sufficient for its CaCC activity. The C-terminal region has low sequence identity. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal domain altering the electrophysiological properties of the channel [,
].This entry also includes uncharacterised proteins belonging to protein family UPF0187.
This entry represents a family plant proteins, including At3g61320 from Arabidopsis thaliana (also known as ATVCCN1 or BESTROPHIN-LIKE PROTEIN), which is a chloride channel required for ion transport and homeostasis across the thylakoid membrane to adjust photosynthesis according to the light environment [
,
,
].
This entry describes the riboflavin biosynthesis protein (ribD) as found in Escherichia coli. The N-terminal domain includes the conserved zinc-binding site region that is shared by proteins such as cytosine deaminase, mammalian apolipoprotein B mRNA editing protein, blasticidin-S deaminase, and Bacillus subtilis competence protein comEB. The C-terminal domain is homologous to the full length of yeast HTP reductase, a protein required for riboflavin biosynthesis. A number of archaeal proteins that may be related to the riboflavin biosynthesis protein contain only the C-terminal domain.
The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.
The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.This entry includes subunit Med31 of the Mediator complex and the Saccharomyces cerevisiae homologue, Soh1. Soh1 is responsible for the repression of temperature sensitive growth of the Hpr1 mutant [
] and has been found to be a component of the RNA polymerase II transcription complex. Soh1 not only interacts with factors involved in DNA repair, but transcription as well. Thus, the Soh1 protein may serve to couple these two processes [].Med31 is organised as a four helix bundle and with the N-terminal part of subunit Med7 forms a submodule of the middle module of the mediator core which is unique in structure and function. In vivo, Med7N/31 has a predominantly positive function on the expression of a specific subset of genes, including genes involved in methionine metabolism and iron transport [
].
This protein family includes a variety of substrate carrier proteins that are involved in energy transfer and are found in the inner mitochondrial membrane [
,
,
,
,
]. UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation. As a result, energy is dissipated in the form of heat.Mitochondrial brown fat uncoupling protein 1 from chordates (UCP1) from chordates is responsible for thermogenic respiration, a specialised capacity of brown adipose tissue to the regulation of energy balance. It regulates the production of reactive oxygen species/ROS by mitochondria [
,
].The protein has a tripartite structure, with each of the 3 similar domains displaying a transmembrane helix, a loop, an amphipathic helix and another transmembrane helix. Overall, it shows a channel-like structure [
].The domains exhibit striking conservation of several residues, especially
of glycine and proline, which may constitute structurally strategicpositions [
].
This group represents a phosphoacetylglucosamine mutase (PAGM; also known as phosphoglucomutase 3 or N-acetylglucosamine-phosphate mutase [
]). It is an essential enzyme found in eukaryotes that reversibly catalyzes the conversion of GlcNAc-6-phosphate into GlcNAc-1-phosphate as part of the UDP-N-acetylglucosamine (UDP-GlcNAc) biosynthetic pathway. UDP-GlcNAc is an essential metabolite that serves as the biosynthetic precursor of many glycoproteins and mucopolysaccharides. PAGM is a member of the alpha-D-phosphohexomutase superfamily [], which catalyzes the intramolecular phosphoryl transfer of sugar substrates []. The alpha-D-phosphohexomutases have four domains with a centrally located active site formed by four loops, one from each domain []. All four domains are included in this alignment model.
The ~250-residue pterin-binding domain has been shown to adopt a (beta/alpha)8 barrel fold, which has the overall shape of a distorted cylinder. It has eight α-helices stacked around the outside of an inner cylinder of parallel β-strands. The pterin ring binds at the bottom of the (beta/alpha;)8 barrel in a polar cup-like region that is relatively solvent exposed and fairly negatively charged. The pterin ring is partially buried within the (beta/alpha)8 barrel. The pterin binding residues are highly conserved and include aspartate and asparagine residues located at the C terminus of the β-strands of the barrel, which are predicted to form hydrogen bonds with the nitrogen and oxygen atoms of the pterin ring [
,
,
].Some proteins known to contain a pterin-binding domain are listed below:
Prokaryotic and eukaryotic B12-dependent methionine synthase (MetH) (
), a large, modular protein that catalyzes the transfer of a methyl group from methyltetrahydrofolate (CH3-H4folate) to Hcy to form methionine, using cobalamin as an intermediate methyl carrier.
Prokaryotic and eukaryotic dihydropteroate synthase (DHPS) (
). It catalyzes the condensation of para-aminobenzoic acid (pABA) with 7,8- dihydropterin-pyrophosphate (DHPPP), eliminating pyrophosphate to form 7,8- dihydropteroate which is subsequently converted to tetrahydrofolate.
Moorella thermoacetica 5-methyltetrahydrofolate corrinoid/iron sulphur protein methyltransferase (MeTr). It transfers the N5-methyl group from CH3-H4folate to a cob(I)amide centre in another protein, the corrinoid iron sulphur protein.
This domain is present in sequences representing dihydropteroate synthase, the enzyme that catalyzes the second to last step in folic acid biosynthesis.Dihydropteroate synthase (
) (DHPS), a functional homodimer, catalyses the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid to form 7,8-dihydropteroate. This is the second step in the three-step pathway leading from 6-hydroxymethyl-7,8-dihydropterin to 7,8-dihydrofolate. DHPS is the target of sulfonamides, which are substrate analogues that compete with para-aminobenzoic acid. Bacterial DHPS (gene sul or folP) [
] is a protein of about 275 to 315 amino acid residues that is either chromosomally encoded or found on various antibiotic resistance plasmids. In the lower eukaryote Pneumocystis carinii, DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas) [].Prokaryotes (and some lower eukaryotes) must synthesize folate de novo, while higher eukaryotes are able to utilize dietary folate and therefore lack DHPS.
All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesise folate
de novobecause they lack the active transport system of higher vertebrate cells which allows these organisms to use dietary folates. Enzymes involved in folate biosynthesis are therefore targets for a variety of antimicrobial agents such as trimethoprim or sulphonamides. 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (
) (HPPK) catalyses the attachment of pyrophosphate to 6-hydroxymethyl-7,8-dihydropterin to form 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. This is the first step in a three-step pathway leading to 7,8 dihydrofolate. Bacterial HPPK (gene folK or sulD) [
] is a protein of 160 to 270 amino acids. In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas) [].
All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. The enzyme 7,8-dihydropteroate synthase (DHPS) (
) catalyses the condensation of para-aminobenzoic acid (pABA) with 6-hydroxymethyl-7, 8-dihydropterin-pyrophosphate to form 7,8-dihydropteroate and pyrophosphate. DHPS is essential for the de novo synthesis of folate in prokaryotes, lower eukaryotes, and in plants, but is absent in mammals [
]. By contrast, higher vertebrates possess an active transport system that enables them to use dietary folates. DHPS is the target of sulphonamides, which are substrate analogues that compete with pABA, but which do not affect vertebrates as they lack the DHPS enzyme. DHPS is a single domain protein that forms an eight-stranded TIM alpha/beta barrel, where the 7,8-dihydropterin pyrophosphate substrate binds in a deep cleft in the barrel []. In the lower eukaryote Pneumocystis carinii, DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas) [].Other proteins contain a DHPS-like domain, including members of the methyltetrahydrofolate (corrinoid iron-sulphur protein methyltransferase (MeTr)) family. MeTr catalyses a key step in the Wood-Ljungdahl pathway of carbon dioxide fixation [
]. Other members of this family that contain a DHPS-like domain include methionine synthase and methanogenic enzymes that activate the methyl group of methyltetrahydromethano(or -sarcino)pterin.
This domain is characteristic of the enzymes 6-phosphogluconolactonase (
), Glucosamine-6-phosphate isomerase (
), and Galactosamine-6-phosphate isomerase. 6-Phosphogluconolactonase is the enzyme responsible for the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate, the second step in the pentose phosphate pathway. Glucosamine-6-phosphate isomerase (or Glucosamine 6-phosphate deaminase) is the enzyme responsible for the conversion of D-glucosamine 6-phosphate into D-fructose 6-phosphate [
]. It is the last specific step in the pathway for N-acetylglucosamine (GlcNAC) utilization in bacteria such as Escherichia coli (gene nagB) or in fungi such as Candida albicans (gene NAG1).
6-phosphogluconolactonases (6PGL)
, which hydrolyses 6-phosphogluconolactone to 6-phosphogluconate is one of the enzymes in the pentose phosphate pathway. Two families of structurally dissimilar 6PGLs are known to exist: the Escherichia coli (strain K12) YbhE
[
] and the Pseudomonas aeruginosa DevB [
] types. 6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate.This entry refers to the DevB type of 6-phosphogluconolactonase.
The RimP protein (also known as YlxS in Bacillus subtilis) facilitates maturation of the 30S ribosomal subunit, and is required for the efficient production of translationally competent ribosomes [
].
Proteins in this entry are members of the glucose-methanol-choline oxidoreductase family of flavoenzymes [
]. These enzymes catalyse diverse reaction and include glucose dehydrogenase (), alcohol oxidase (
), glucose oxidase (
), choline dehydrogenase (
), and cyclase atC from Aspergillus terreus which oxidizes terremutin to terreic acid, a quinone epoxide inhibitor of a tyrosine kinase [
]. Structural studies indicate that these proteins are composed of an N-terminal FAD-binding domain, and a C-terminal substrate-binding domain [
,
,
]. The FAD-binding domain forms the α-β fold typical of dinucleotide binding proteins, while the substrate-binding domain consists of a β-sheet surrounded by α-helices. The general topology of these proteins is conserved, though inserted structural elements occur in both choline dehydrogenase and alcohol dehydrogenase [].
The ~60-residue RAP (an acronym for RNA-binding domain abundant in Apicomplexans) domain is found in various proteins in eukaryotes. It is particularly abundant in apicomplexans and might mediate a range of cellular functions through its potential interactions with RNA [
].The RAP domain consists of multiple blocks of charged and aromatics residues and is predicted to be composed of α-helical and β-strand structures. Two predicted loop regions that are dominated by glycine and tryptophan residues are found before and after the central β-sheet [
].Some proteins known to contain a RAP domain are listed below: Human hypothetical protein MGC5297, Mammalian FAST kinase domain-containing proteins (FASTKDs), Chlamydomonas reinhardtii chloroplastic trans-splicing factor Raa3.
This entry represents a haem-binding domain with a 4-helical bundle structure that is found in transmembrane di-haem cytochromes. The domain contains four transmembrane helices in an up-and-down bundle, and binds two haem groups in between the helices; three of the four haem-binding residues is conserved between family members. Proteins containing this domain include:N-terminal domain of mitochondrial cytochrome b subunit, in which the domain contains an extra transmembrane linker helix that is absent in plant and cyanobacteria subunits [
].Cytochrome b6 subunit of the cytochrome b6f complex, which provides the electronic connection between the photosystems I and II reaction centres of oxygenic photosynthesis, and generates a transmembrane electrochemical proton gradient for adenosine triphosphate synthesis [
].Cytochrome gamma subunit of formate dehydrogenase-N (Fdn-N), which acts as a major component of Escherichia coli nitrate respiration [
].Please note, this entry also identifies a number of proteins that are cleaved into two chains - a truncated non-functional cytochrome oxidase 1 and an intron-encoded endonuclease.
In the mitochondrion of eukaryotes and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III (
) - also known as the bc1 complex or ubiquinol-cytochrome c reductase. In plant chloroplasts and cyanobacteria, there is a analogous protein, cytochrome b6, a component of the plastoquinone-plastocyanin reductase (
), also known as the b6f complex.
Cytochrome b/b6 [
,
] is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part.Cytochrome b/b6 non-covalently binds two haem groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two haem groups.
Apart from regions around some of the histidine haem ligands, there are a few conserved regions in the sequence of b/b6. The best conserved of these regions includes an invariant P-E-W triplet which lies in the loop that separates the fifth and sixth transmembrane segments. It seems to be important for electron transfer at the ubiquinone redox site - called Qz or Qo (where o stands for outside) - located on the outer side of the membrane. This entry represents the N-terminal region of these proteins.
Cytochrome b/b6 [
,
] is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part. Cytochrome b/b6 non-covalently binds two haem groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two haem groups [,
].
This domain is found in members of the Dicer protein family which function in RNA interference, an evolutionarily conserved mechanism for gene silencing using double-stranded RNA (dsRNA) molecules. It is essential for the activity of Dicer [
,
]. It is a divergent double stranded RNA-binding domain []. The N-terminal alpha helix of this domain is in a different orientation to that found in canonical dsRNA-binding domains. This results in a change of charge distribution at the potential dsRNA-binding surface and in the N- and C-termini of the domain being in close proximity []. This domain has weak dsRNA-binding activity. It mediates heterodimerisation of Dicer proteins with their respective protein partners [].
The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm5 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring [
]. MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication [,
,
]. During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation [].The components of the MCM2-7 complex are: DNA replication licensing factor MCM2, DNA replication licensing factor MCM3, DNA replication licensing factor MCM4, DNA replication licensing factor MCM5, DNA replication licensing factor MCM6, DNA replication licensing factor MCM7,
Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, gene
expression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotide exchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with an adjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct andsmaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cell migration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DHR-2 domain (also termed the CZH2 or DOCKER domain), [
,
,
,
,
,
].The ~200 residue DOCK-type C2 domain is located toward the N terminus. It adopts a C2-like architecture and interacts with phosphatidylinositol
3,4,5-trisphosphate [] to mediate signalling and membrane localization. The central core of the DOCK-type C2 domain domain adopts an antiparallel β-sandwich with the "type II"C2 domain fold (a circular permutation of the more common "type I"topology), in which two 4-stranded sheets with strand order 6-5-2-3 and 7-8-1-4 create convex- and concave-exposed faces, respectively [
].Some DOCK proteins are listed below:Mammalian Mammalian dedicator of cytokinesis 180 (DOCK180 or DOCK1),
important for cell migration.Mammalian DOCK2, important for lymphocyte development, homong, activation,
adhesion, polarization and migration processes.Mammalian DOCK3 (also known as MOCA), is expressed predominantly in neurons
and resides in growth cones and membrane ruffles.Mammalian DOCK4, possesses tumor suppressor properties.
Mammalian DOCK9 (zizimin1), plays an important role in dendrite growth in
hippocampal neurons through activation of Cdc42.Drosophila melanogaster Myoblast city.
Caenorhabditis elegans CED-5.
Initiation factor 2 (IF-2) (gene infB) [
] is one of the three factorsrequired for the initiation of protein biosynthesis in bacteria. IF-2
promotes the GTP-dependent binding of the initiator tRNA to the small subunitof the ribosome. IF-2 is a protein of about 70 to 95 Kd which contains a
central GTP-binding domain flanked by a highly variable N-terminal domain anda more conserved C-terminal domain.
Bacterial IF-2 is structurally and functionally related to eukaryoticmitochondrial IF-2 (IF-2(mt)) [
] as well as to algal and plants chloroplastIF-2 (IF-2(chl)). Both IF-2(mt) and IF-2(chl) are encoded by nuclear genes and
are produced as precursor proteins with a transit peptide. An exception arered algae where IF-2(chl) is encoded by the plastid genome [
].This model discriminates eubacterial (and mitochondrial) translation initiation factor 2 (IF-2), encoded by the infB gene in bacteria, from similar proteins in the Archaea and Eukaryotes. In the bacteria and in organelles, the initiator tRNA is charged with N-formyl-Met instead of Met. This translation factor acts in delivering the initator tRNA to the ribosome. It is one of a number of GTP-binding translation factors recognised by the pfam HMM GTP_EFTU.
Initiation factor 2 (IF-2) is one of the three factors required for the initiation of protein biosynthesis in bacteria [
]. IF-2 promotes the GTP-dependent binding of the initiator tRNA to the small subunit of the ribosome. IF-2 is a protein of about 70 to 95kDa that contains a central GTP-binding domain flanked by a highly variable N-terminal domain and a more conserved C-terminal domain. Some members of this group undergo protein self splicing that involves a post-translational excision of the intein followed by peptide ligation.The function of IF-2 in facilitating the proper binding of initiator methionyl-tRNA to the ribosomal P site appears to be universally conserved [
].This entry represents the domain 3 of IF-2. It consists of a α/β/α structure with a core formed by a parallel β-sheet of 4 strands [
].
This region is found in the N-terminal half of translation initiation factor IF-2. It is found in two copies in IF-2 alpha isoforms, and in only one copy in the N-terminally truncated beta and gamma isoforms [
]. Its function is unknown.
Phosphoribulokinase (PRK)
catalyses the ATP-dependent phosphorylation of
ribulose-5-phosphate to ribulose-1,5-phosphate, a key step in the pentose phosphate pathway where carbon dioxide is assimilated by autotrophic organisms [
]. In general, plant enzymes are light-activated by the thioredoxin/ferredoxin system, while
those from photosynthetic bacteria are regulated by a system that has an absolute
requirement for NADH. Thioredoxin/ferredoxin regulation is mediated by the reversibleoxidation/reduction of sulphydryl and disulphide groups. In the spinach enzyme (
) the
participating residues are Cys-16 and Cys-55. Sequence analysis shows the first of these cysteines to be present in the ATP-binding site [
]; neither is found in the bacterial sequences.
Chlororespiratory reduction 6 is a factor required for the assembly or stabilisation of the chloroplast NAD(P)H dehydrogenase complex in Arabidopsis [
].
This superfamily represents the N-terminal winged helix domain of the vps25 subunit (vacuolar protein sorting-associated protein 25) of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs) [
]. ESCRT-II recruits the transport machinery for protein sorting at MVB []. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo [].ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps35 [
].
This entry represents the Vps25 subunit (vacuolar protein sorting-associated protein 25) of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs) [
]. ESCRT-II recruits the transport machinery for protein sorting at MVB []. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo [].ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps35 [
].
This domain was named after the yeast Sec63 (or NPL1) (also known as the Brl domain) protein in which it was found. This protein is required for assembly of functional endoplasmic reticulum translocons [
,
]. Other yeast proteins containing this domain include pre-mRNA splicing helicase BRR2, HFM1 protein and putative helicases.
The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.
The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.Med12 is a component of the evolutionarily conserved Mediator complex [
]. The Med12 subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway. Med12 is a negative regulator of the Gli3-dependent sonic hedgehog signaling pathway via its interaction with Gli3 within the Mediator. A complex is formed between Med12, Med13, CDK8 and CycC which is responsible for suppression of transcription [].
This family of proteins includes snapin, which is associated with the SNARE complex that mediates synaptic vesicle docking and fusion [
]. This family also includes the yeast snapin-like protein, Snn1, which is a part of a complex involved in endosomal cargo sorting [], and pallidin - a component of a complex involved in biogenesis of lysosome-related organelles [].
PER1 is required for GPI-phospholipase A2 activity and is involved in lipid remodelling of GPI-anchored proteins [
]. PER1 is part of the CREST superfamily []. Human PERLD1 is a functional homologue of PER1, and is also known as PGAP3. Mutations in PGAP3 cause hyperphosphatasia with mental retardation syndrome [].
Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures [
]. The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility []. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. It promotes homologous recombination (HR) repair in response to DNA damage, leading to drive motility of double-strand breaks (DSBs) []. In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein []. Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 [], and crystal structures of the Arp2/3 complex have been solved [].The human complex consists of Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This family represents the ARPC3/p21-ARC subunit.
This endosulphine family includes cAMP-regulated phosphoprotein 19 (ARPP-19), alpha endosulphine and protein Igo1. No function has yet been assigned to ARPP-19 [
]. Endosulphine is the endogenous ligand for the ATP-dependent potassium channels which occupy a key position in the control of insulin release from the pancreatic beta cell by coupling cell polarity to metabolism [].Igo1 is required for initiation of G0 program. In the absence of stimulatory signals, cells may enter into a reversible quiescence (or G0) state that is typically characterised by low metabolic activity, including low rates of protein synthesis and transcription. Igo proteins associate with the mRNA decapping activator Dhh1, sheltering newly expressed mRNAs from degradation via the 5'-3' mRNA decay pathway, and thereby enabling their proper translation during initiation of the G0 program [].
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. This family represents the low molecular weight intrinsic protein PsbR found in PSII, which is also known as the 10kDa polypeptide. The PsbR gene is found only in the nucleus of green algae and higher plants. PsbR may provide a binding site for the extrinsic oxygen-evolving complex protein PsbP to the thylakoid membrane. PsbR has a transmembrane domain to anchor it to the thylakoid membrane, and a charged N-terminal domain capable of forming ion bridges with extrinsic proteins, allowing PsbR to act as a docking protein. PsbR may be a pH-dependent stabilising protein that functions at both donor and acceptor sides of PSII [
].
Translocase of chloroplast 159/132, membrane anchor domain
Type:
Domain
Description:
This is the membrane-anchor domain of translocase of chloroplast 159, TOC159/132. This domain is present in plants at the C terminus of the GTPase, AIG1, and anchors the GTPas region to the outer membrane of the chloroplast. The domain may carry a very C-terminal sequence motif that resembles a transit peptide [
].
This entry represents the translocase of chloroplast 159 family of proteins (Tocs), GTPases involved in protein precursor import into chloroplasts, which recognise chloroplast-destined precursor proteins and regulate their presentation to the translocation channel through GTP hydrolysis [
]. They have three domains: the N-terminal A-domain is acidic, repetitive, weakly conserved, readily removed by proteolysis during chloroplast isolation, not required for protein translocation [,
], and the other domains are designated G (GTPase) and M (membrane anchor) []. The signature for this family includes most of the G domain and all of M. There are at least two distinct Toc159 subtypes, Toc159 and Toc132/Toc120. Toc159 is expressed in young photosynthetic tissues and seems to be specialised in the import of nuclear encoded photosynthetic preproteins from the cytoplasm to the chloroplast, whereas Toc132/Toc120 are expressed relatively prominent in nonphotosynthetic tissues and seem to be specialised in the import of nuclear encoded non-photosynthetic preproteins from the cytoplasm to the chloroplast [].
In eukaryotes and archaea, the e/aIF2 factor is involved in the initiation of protein biosynthesis. In its GTP bound form, e/aIF2 delivers methionylated initiator tRNA to the small subunit of the ribosome. After the pairing between the AUG initiation codon on mRNA and the CAU anticodon of the initiator tRNA, GTP is hydrolysed and e/aIF2:GDP is released from the ribosome. In eukaryotes, eIF2B acts as the guanine nucleotide exchange factor for eIF2. Archaea have no equivalent of eIF2B, and the exchange between GDP and GTP is thought to be spontaneous [
]. eIF2 is composed of three subunits, alpha, beta and gamma. The gamma subunit forms the core of the heterotrimer and confers both tRNA binding and GTP/GDP binding [].This entry represents the C-terminal domain of the gamma subunit of eukaryotic translation initiation factor 2 (eIF2-gamma) found in Eukaryota and Archaea. This domain has a beta barrel structure with Greek key topology. It is required for formation of the ternary complex with GTP and initiator tRNA [
].
In budding yeasts, NatC N(alpha)-terminal acetyltransferases contain Mak10, Mak31 and Mak3 subunits. All three subunits are associated with each other to form the active complex [
]. Human Naa35 is an auxillary component of the NatC complex which catalyzes acetylation of N-terminal methionine residues. It is involved in regulation of apoptosis and proliferation of smooth muscle cells [
].
Sucrose occupies a central position in the metabolic pathways of all plants and plays a variety of roles including transport sugar, storage reserve, compatible solute, and signal compound [
]. This compound is produced by the combined action of two enzymes, sucrose-phosphate synthase () and sucrose-phosphate phosphatase (
), via the intermediate sucrose 6-phosphate. Several studies have shown a positive correlation between sucrose-phosphate synthase activity and plant growth rate and yield in agronomically important plants, though direct proof of a causal link is lacking.
This entry represents sucrose-phosphate synthase from plants, which is known to exist in multigene families in several species of both monocots and dicots. The enzyme contains an N-terminal domain glucosyltransferase domain, a variable linker region, and a C-terminal domain similar to that of sucrose-phosphate phosphatase, the next and final enzyme of sucrose biosynthesis. The C-terminal domain is likely to serve a binding - not a catalytic - function, as sucrose-phosphate phosphatase is always encoded by a distinct protein.
This entry represents a conserved region of the sucrose phosphate phosphohydrolase (SPP) from plants [
,
]. SPP is a member of the Class IIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. SPP catalyses the final step in the biosynthesis of sucrose, a critically important molecule for plants. Sucrose phosphate synthase (SPS), the prior step in the biosynthesis of sucrose contains a domain which exhibits considerable similarity to SPP albeit without conservation of the catalytic residues. The catalytic machinery of the synthase resides in another domain. It seems likely that the phosphatase-like domain is involved in substrate binding, possibly binding both substrates in a "product-like"orientation prior to ligation by the synthase catalytic domain. This domain is also found in bacterial proteins.
This entry includes Iojap protein from plants, the ribosomal silencing factor RsfS (also known as RsfA) from bacteria and its homologue, C7orf30, from animals. In plants, there are Iojap protein in plastid and Iojap related protein in mitochondria. Plastid Iojap is involved in plastid biogenesis in plants [
], while mitochondrial Iojap related protein may be a ribosome silencing factor involved in organelle biogenesis and required for germination []. RsfS functions as a ribosomal silencing factor. It interacts with ribosomal protein L14 (rplN), blocking formation of intersubunit bridge B8, preventing association of the 30S and 50S ribosomal subunits and the formation of functional ribosomes, thus repressing translation [
]. C7orf30 associates with the large subunit of the mitochondrial ribosome and is involved in translation [
].
The HORMA domain (for HOP1, REV7 and MAD2) is an about 180-240 amino acids region containing several conserved motifs. Whereas the MAD2 and the REV7 proteins are almost entirely made up of HORMA domains, HOP1 contains a HORMA domain in its N-terminal region and a Zn-finger domain, whose general arrangement of metal-chelating residues is similar to that of the PHD finger, in the C-terminal region. The HORMA domain is found in proteins showing a direct association with chromatin of all crown group eukaryotes. It has been suggested that the HORMA domain recognises chromatin states that result from DNA adducts, double-stranded breaks or non-attachment to the spindle and acts as an adaptor that recruits other proteins involved in repair [
].Secondary structure prediction suggests that the HORMA domain is globular and could potentially form a complex β-sheet(s) with associated α-helices [
].Some proteins known to contain a HORMA domain are listed below:Eukaryotic HOP1, a conserved protein that is involved in meiotic-synaptonemal-complex assembly.Eukaryotic mitotic-arrest-deficient 2 protein (MAD2), a key component of the mitotic-spindle-assembly checkpoint [
].Eukaryotic REV7, a subunit of the DNA polymerase zeta that is involved in translesion, template-independent DNA synthesis.
Rfa1 (also known as RPA70) is a component of the replication protein A (RPA) complex, which binds to and removes secondary structure from ssDNA. The RPA complex is involved in DNA replication, repair, and recombination [
].
This superfamily represents an α-helical domain is found between the S1 N-terminal domain and the α-β C-terminal domain in the alpha subunit of translation initiation factor 2 [
]. It consists of a bundle of two orthogonally packed alpha-hairpins.
In Eukaryota and Archaea, translation initiation factor 2 (eIF2/aIF2), which contains three subunits (alpha, beta and gamma), is pivotal for binding of charged initiator tRNA to the small ribosomal subunit. This entry represents the alpha subunit of both eukaryota and archaeal translation initiator factor 2.
This superfamily represents the C-terminal domain of the translation initiation factor 2 alpha subunit. It adopts an α-β fold, containing five beta strands, two alpha helices, and one loosely associated C-terminal alpha helix [
].
This entry represents a domain found in Pat1 and its homologues. Pat1 is involved in translational repression and enhanced mRNA decay. It is part of the Lsm1-7-Pat1 complex that plays a role in activation of deadenylation-dependent decapping in the 5' to 3' pathway and in the protection of mRNA 3' ends [
].There are two Pat1 homologues in vertebrates, Pat1a and Pat1b, in contrast to the single protein in yeast and invertebrates. The maternally expressed Pat1a protein acts as a translational repressor, while Pat1b functions in mRNA decay in somatic cells. Pat1b is localised to P-body and is a nucleocytoplasmic shuttling protein that may perform various nuclear functions upstream of their multiple posttranscriptional regulatory roles in the cytoplasm [
].
Vps52 complexes with Vps53 and Vps54 to form the Golgi-associated retrograde protein (GARP) complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network, regulating membrane trafficking events [
,
,
]. It is also part of the EARP (Endosome-Associated Recycling Protein) complex, involved in endocytic recycling [].
Dual-specificity RNA methyltransferase RlmN specifically methylates position 2 of adenine 2503 in 23S rRNA, which serves to optimize ribosomal fidelity, and position 2 of adenine 37 in tRNAs. Unmodified tRNA is not a suitable substrate for RlmN, which suggests that RlmN works in a late step during tRNA maturation [
,
,
].
Ribosomal RNA large subunit methyltransferase RlmN/Cfr
Type:
Family
Description:
This entry represents the RlmN family, that includes dual-specificity RNA methyltransferase RlmN and ribosomal RNA large subunit methyltransferase Cfr.Dual-specificity RNA methyltransferase RlmN specifically methylates position 2 of adenine 2503 in 23S rRNA [
]. This nucleotide is located in a functionally important region of the ribosome, at the entrance to the nascent peptide exit tunnel, and may thus be involved in the interaction with the nascent peptide. It also methylates position 2 of adenine 37 in tRNAs. Unmodified tRNA is not a suitable substrate for RlmN, which suggests that RlmN works in a late step during tRNA maturation [,
,
].Ribosomal RNA large subunit methyltransferase Cfr specifically methylates position 8 of adenine 2503 in 23S rRNA. It can also methylate position 2 of A2503 after the primary methylation is complete, to form 2,8-dimethyladenosine. Cfr confers antibiotic resistance in bacteria. The antibiotic resistance is provided by methylation at the 8 position and is independent of methylation at the 2 position of A2503 [
,
].
The AP-3 complex functions in cargo-selective protein transport from the Golgi to the vacuole/lysosome [
]. It is an adapter-related complex which is thought not to be clathrin-associated. The AP-3 complex facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to the vacuole. It is required for the transport via the ALP pathway []. In neurons, AP-3 generates synaptic vesicles or vesicles carrying synaptic vesicle membrane proteins [].This entry represents the beta subunit of the AP-3 complex.
Adaptor protein (AP) complexes function in protein transport via transport vesicles in different membrane traffic pathways. AP complexes are involved in the formation of clathrin-coated vesicles (CCVs) by recruiting the scaffold protein, clathrin. AP complexes are also involved in the cargo selection by recognising the sorting signals in proteins. Several AP complexes have been identified: AP-2 mediates endocytosis from the plasma membrane, while AP-1, AP-3 and AP-4 play a role in the endosomal/lysosomal sorting pathways [
,
]. AP complexes are heterotetramers which consist of two large subunits, one medium subunit and one small subunit. One of the large subunits (alpha, gamma, delta and epsilon) mediates binding to the target membrane. The other large subunit (beta) recruits clathrin through the clathrin-binding sequence []. This entry represents the AP complexes beta subunit.
